rs1555901135

chrX-13738871-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_003611.3(OFD1):c.338A>G(p.Gln113Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000935 in 1,069,359 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.4e-7 (0 hom. 0 hem.)
• Consequence: OFD1 NM_003611.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.01

Genes affected

OFD1 (HGNC:2567): (OFD1 centriole and centriolar satellite protein) This gene is located on the X chromosome and encodes a centrosomal protein. A knockout mouse model has been used to study the effect of mutations in this gene. The mouse gene is also located on the X chromosome, however, unlike the human gene it is not subject to X inactivation. Mutations in this gene are associated with oral-facial-digital syndrome type I and Simpson-Golabi-Behmel syndrome type 2. Many pseudogenes have been identified; a single pseudogene is found on chromosome 5 while as many as fifteen have been found on the Y chromosome. [provided by RefSeq, Aug 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.872

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OFD1	NM_003611.3	c.338A>G	p.Gln113Arg	missense_variant	4/23	ENST00000340096.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OFD1	ENST00000340096.11	c.338A>G	p.Gln113Arg	missense_variant	4/23	1	NM_003611.3	P1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.35e-7 AC: 1 AN: 1069359 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 340759

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000122

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Athena Diagnostics

Jul 13, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.29	T;.
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.73	T;T
M_CAP	Pathogenic	0.67	D
MetaRNN	Pathogenic	0.87	D;D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Uncertain	2.7	M;M
MutationTaster	Benign	0.99	D;D;D;D
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-2.3	N;N
REVEL	Pathogenic	0.78
Sift	Uncertain	0.0040	D;D
Sift4G	Benign	0.22	T;T
Polyphen		1.0	D;D
Vest4		0.60
MutPred		0.47		Loss of ubiquitination at K116 (P = 0.0273);Loss of ubiquitination at K116 (P = 0.0273);
MVP		0.99
MPC		0.56
ClinPred		0.95	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.57
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1555901135; hg19: chrX-13756990;